There is apparent widespread acceptance of universal laboratory screening for GDM in the U.S., despite both the 2001 ACOG Technical Bulletin on Gestational Diabetes and the Fourth International Workshop-Conference on Gestational Diabetes failing to endorse this practice (4,18). The clinical dilemma of GDM was summarized during the Fourth International Workshop-Conference, which concluded that "although there is a general consensus that prevalence of GDM is increasing globally, there is considerable controversy about the clinical importance of GDM and the magnitude of its impact on mother and offspring" (14,18). Similarly, the Canadian Task Force on Periodic Health Examination stated that "further research is needed to establish the relative risk of neonatal and perinatal illness in relation to various degrees of sub-diabetic elevations in maternal blood glucose levels. The quality of available evidence cannot support a recommendation to include universal screening for gestational diabetes" (15). Instead, this panel suggested that a decision to proceed with screening for this diagnosis must be made on other nonspecific grounds. This vague recommendation was accompanied by an admission that the Task Force recognized that a proportion of women with various degrees of carbohydrate intolerance during pregnancy will have adverse outcomes and might benefit from screening. In 2003, the U.S. Preventative Services Task Force acknowledged that no well-conducted randomized controlled trial existed that provided direct evidence for the health benefits of screening for GDM (2). Whereas insulin therapy may decrease the incidence of fetal macrosomia in those pregnancies complicated by significant hyperglycemia, the magnitude of any effect on maternal and neonatal health remains uncertain. Moreover, the Task Force report noted that insufficient evidence exists to determine if a health benefit accompanies treatment for the large number of women with GDM with milder degrees of hyperglycemia. A randomized controlled trial is necessary to answer this question (2). With mild GDM affecting 1-3% of pregnancies, ∼50-100,000 women annually are being identified and treated for this diagnosis, making this an important clinical issue. Most recently, Crowther et al. (19) reported results on a 10-year multicenter randomized trial designed to determine whether treatment of GDM reduces the risk of perinatal complications. The primary outcome of this study was a composite of perinatal morbidity and mortality (stillbirth, shoulder dystocia, bone fractures, nerve palsy, neonatal intensive care unit admission, and jaundice). The authors found the composite rate of "serious" perinatal complications was lower among the infants of the 490 treated women compared with the 510 infants in the routine care group (1 vs. 4%). This study represents the first large-scale randomized treatment trial for GDM. The sample size is remarkably similar to the ongoing MFMU trial; however, the Crowther study is different with respect to design and analysis of outcome data. Most importantly, the criteria used for the Crowther study include women with more significant hyperglycemia than the MFMU trial. Thus, our study should provide additional information regarding the effect of treatment of women with milder GDM. The perinatal outcome composite in Crowther's study includes shoulder dystocia, a subjective diagnosis, which in turn weighed heavily on the composite difference observed among study groups. An increased rate of admission to the neonatal intensive care unit was observed in the treatment group; however, no difference was observed in the rate of hypoglycemia (secondary outcome) requiring intravenous therapy. Finally, details regarding several antepartum stillbirths suggest these may not have been related to untreated GDM such that the overall conclusion of a reduction in "serious" perinatal complications in treated GDM must be interpreted with caution. In contrast to the Crowther study, the MFMU Network trial primary outcome includes two markers of fetal response to maternal hyperglycemia: neonatal hypoglycemia and cord C-peptide levels. These outcomes should allow for a meaningful interpretation of any treatment effect in the subset of GDM with mild disease. To date, few additional studies have examined the effectiveness of intensive treatment among women with mild GDM. A summary of four trials including 612 women with mild GDM found no benefit in dietary treatment in preventing adverse health outcomes (20). The ongoing population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study is designed to determine levels of carbohydrate intolerance during pregnancy associated with adverse perinatal outcomes. Specifically, at what level of maternal glycemia is there fetal and/or maternal risk? A continuum of risk is anticipated as a likely result in the Hyperglycemia and Adverse Pregnancy Outcome study. The previously cited Crowther study and the ongoing MFMU trial address whether treatment of GDM is effective at reducing perinatal risk. Given that the MFMU Network trial considers only women with normal fasting glucose levels, it should help clarify whether a benefit exists to treatment of mild GDM. The trial should also complement the Hyperglycemia and Adverse Pregnancy Outcome study data in arriving at some consensus for selecting thresholds for diagnosis and treatment of carbohydrate intolerance during pregnancy.
[Show abstract][Hide abstract] ABSTRACT: Mothers with gestational diabetes mellitus (GDM) are at high lifetime risk of developing type 2 diabetes mellitus. The magnitude of risk for cardiovascular disease after GDM is less well established. Recently, intervention trials using lifestyle modification or medications used to treat type 2 DM have successfully prevented/delayed development of DM in women after GDM. Offspring of mothers with GDM are at risk for development of obesity and abnormal glucose metabolism during childhood, adolescence, and adulthood. Factors responsible for these risks are not fully understood. Having fetal hyperinsulinism is a risk factor for development of both obesity and abnormal glucose metabolism, and might be implicated in pathophysiology. It remains to be established whether the long-term effects of exposure to diabetes mellitus during intrauterine development can be prevented.
[Show abstract][Hide abstract] ABSTRACT: For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glu- cose level of 1 SD (6.9 mg per deciliter (0.4 mmol per liter)), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter (1.7 mmol per liter)), and an in- crease in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter (1.3 mmol per liter)). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval (CI), 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesar- ean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Sig- nificant associations were also observed for secondary outcomes, although these tended to be weaker. CONCLUSIONS Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood se- rum C-peptide levels.
New England Journal of Medicine 04/2008; 358(19):1991-2002. · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically reviewed evidence on outcomes of gestational weight gain and their confounders and effect modifiers, outcomes of weight gain within or outside the 1990 Institute of Medicine (IOM) guidelines, risks and benefits of weight gain recommendations, and anthropometric measures of weight gain.
We searched MEDLINE Cochrane Collaboration resources, Cumulative Index to Nursing & Allied Health Literature, and Embase.
We included studies published in English from 1990 through October 2007. We excluded studies with low sample size (based on study design: case series <100 subjects and cohorts <40 subjects).
Overall, strong evidence supported an association between gestational weight gains and the following outcomes: preterm birth, total birthweight, low birthweight (<2,500 g), macrosomia, large-for-gestational-age (LGA) infants, and small-for-gestational-age (SGA) infants; moderate evidence supported an association for cesarean delivery and intermediate-term weight retention (3 months to 3 years postpartum). The studies reviewed provided strong evidence for the independent association of pregravid weight status and outcomes, moderate evidence for age and parity, and weak evidence for race. Regarding outcomes of weight gain within or outside 1990 IOM guidelines, moderate to strong evidence suggests an association between weight gain below IOM recommendations and preterm birth, low birthweight, SGA birthweights, and failure to initiate breastfeeding, and strong evidence for the association between weight gain above IOM recommendations and high birthweight, macrosomia, and LGA birthweights. Moderate evidence supports an association between weight gain above IOM guidelines and cesarean delivery and postpartum weight retention in the short, intermediate, and long term. Included research is inadequate for objective assessments of the range of harms and benefits of providing all women, irrespective of age, race or ethnicity, or pregravid body mass index (BMI), with the same recommendation for weight gain in pregnancy.
Gestational weight gain is associated with some infant and maternal outcomes. One weight gain recommendation for all women is not supported by the evidence identified in this review. To understand fully the impact of gestational weight gain on short- and long-term outcomes for women and their offspring will require that researchers use consistent definitions of weight gain during pregnancy, better address confounders in their analyses, improve study designs and statistical models, and conduct studies with longer followup.
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